Skin cancer risk in CHEK2 mutation carriers

CHEK2 mutations have been linked with an increased risk of breast cancer. A unique challenge for oncodermatologists and oncologists is in the monitoring and counselling of patients regarding skin cancer risk due to CHEK2 mutation carrier status. In this review, we highlight current information in the literature on the risk of melanoma and non-melanoma skin cancers in CHEK2 mutation carriers. On the molecular level, CHEK2 is a cell cycle regulator that has been linked to cancer pathogenesis, though evidence from clinical studies regarding skin cancer risk has been inconsistent and conflicting. For melanoma, one study has demonstrated a statistically significant twofold risk of melanoma in individuals with CHEK2 mutations, particularly the CHEK2*1100delC variant. Five other studies did not show an association. For non-melanoma skin cancer, fewer data exist, with one prevalence study of CHEK2 mutations in a cohort of patients with basal cell carcinomas. Although there are currently no known studies of CHEK2 and cutaneous squamous cell carcinoma (SCC), data from other disciplines associating CHEK2 with head and neck SCCs are emerging. Overall, while there is currently not enough evidence to make conclusive statements regarding increased risk of melanoma and non-melanoma skin cancers in CHEK2 carriers, a molecular mechanism associating the mutation with cutaneous malignancy pathogenesis is evident, and further work is needed. Patient with CHEK2 mutations may benefit from screening dermatologic examinations with particular attention to skin cancers.